Little is known about factors influencing the rate of progression of Alzheimer's dementia. Using data from the Cache County Dementia Progression Study, the authors examined the link between ...clinically significant neuropsychiatric symptoms in mild Alzheimer's dementia and progression to severe dementia or death.
The Cache County Dementia Progression Study is a longitudinal study of dementia progression in incident cases of this condition. Survival analyses included unadjusted Kaplan-Meier plots and multivariate Cox proportional hazard models. Hazard ratio estimates controlled for age at dementia onset, dementia duration at baseline, gender, education level, General Medical Health Rating, and apolipoprotein E epsilon 4 genotype.
Three hundred thirty-five patients with incident Alzheimer's dementia were studied. Sixty-eight (20%) developed severe dementia over the follow-up period. Psychosis (hazard ratio=2.007), agitation/aggression (hazard ratio=2.946), and any one clinically significant neuropsychiatric symptom (domain score ≥4, hazard ratio=2.682) were associated with more rapid progression to severe dementia. Psychosis (hazard ratio=1.537), affective symptoms (hazard ratio=1.510), agitation/aggression (hazard ratio=1.942), mildly symptomatic neuropsychiatric symptoms (domain score of 1-3, hazard ratio=1.448), and clinically significant neuropsychiatric symptoms (hazard ratio=1.951) were associated with earlier death.
Specific neuropsychiatric symptoms are associated with shorter survival time from mild Alzheimer's dementia to severe dementia and/or death. The treatment of specific neuropsychiatric symptoms in mild Alzheimer's dementia should be examined for its potential to delay time to severe dementia or death.
Dementia Oh, Esther S; Rabins, Peter V
Annals of internal medicine,
09/2019, Volume:
171, Issue:
5
Journal Article
Peer reviewed
Alzheimer disease (AD) and other dementia syndromes are becoming more common; an estimated 5.5 million adults aged 65 years or older are living with AD in the United States. It is important for ...primary care physicians to gain knowledge in this field because most community-dwelling older adults receive their care from them. This article discusses the latest findings in approaches to prevent cognitive decline as well as dementia screening, diagnosis, and treatment. Approaches to address quality of life for persons with dementia and their caregivers are also discussed.
Objectives
To determine the prevalence and correlates of unmet needs in a sample of community‐residing persons with dementia (PWD) and their informal caregivers.
Design
Analysis of cross‐sectional, ...baseline participant characteristics before randomization in a care coordination intervention trial.
Setting
Baltimore, Maryland.
Participants
Community‐residing PWD (n = 254) and their informal caregivers (n = 246).
Measurements
In‐home assessments of dementia‐related needs based on the Johns Hopkins Dementia Care Needs Assessment. Bivariate and multivariate regression analyses were conducted to identify demographic, socioeconomic, clinical, functional, and quality‐of‐life correlates of unmet needs.
Results
The mean number of unmet needs was 7.7 ± 4.8 in PWD and 4.6 ± 2.3 in caregivers, with almost all PWD (99%) and caregivers (97%) having one or more unmet needs. Unmet needs in PWD were significantly greater in those with higher cognitive function. Ninety percent of PWD had unmet safety needs, more than half had unmet needs for meaningful activities, and almost one‐third had not received a prior evaluation or diagnosis. Higher unmet needs in PWD was significantly associated with nonwhite race, lower income, less impairment in activities of daily living, and more symptoms of depression. For caregivers, more than 85% had unmet needs for resource referrals and caregiver education. Higher unmet caregiver needs was significantly associated with nonwhite race, less education, and more symptoms of depression.
Conclusion
Many community‐residing PWD and their caregivers have unmet dementia‐related needs for care, services, and support. Providers should be aware that unmet needs may be higher in minority and low‐income community residents, caregivers with lower education, and individuals with early‐stage dementia. Identifying and treating symptoms of depression in PWD and caregivers may enable them to address their other unmet needs.
Primary age-related tauopathy (PART) is a recently described entity that can cause cognitive impairment in the absence of Alzheimer's disease (AD). Here, we compared neuropathological features, tau ...haplotypes, apolipoprotein E (APOE) genotypes, and cognitive profiles in age-matched subjects with PART and AD pathology.
Brain autopsies (n = 183) were conducted on participants 85 years and older from the Baltimore Longitudinal Study of Aging and Johns Hopkins Alzheimer's Disease Research Center. Participants, normal at enrollment, were followed with periodic cognitive evaluations until death.
Compared with AD, PART subjects showed significantly slower rates of decline on measures of memory, language, and visuospatial performance. They also showed lower APOE ε4 allele frequency (4.1% vs. 17.6%, P = .0046).
Our observations suggest that PART is separate from AD and its distinction will be important for the clinical management of patients with cognitive impairment and for public health care planning.
Objectives: Studies of adults with autism spectrum disorder (ASD) have demonstrated poor outcomes related to independence and everyday living skills compared to the general population. In a sample of ...74 adults with ASD who require a high level of support we sought to identify correlates of daily functioning.
Methods: We administered questionnaires to residential staff and identified participants' independence level in basic and instrumental activities of daily living.
Results: There was no association of age with daily functioning. Higher daily functioning was associated with a better general medical health rating. Functional independence was greater in participants with IQ range of 55 to 65 compared to those with IQ below 55. Language difficulties and behavioral disturbances were not significantly correlated with independence in daily living skills. In this sample, individual had held a median of three different types of jobs in supported employment.
Conclusion: Daily functioning in adults with autism generally does not decline with age, but because this was cross-sectional data, this requires further confirmation. Community programs designed for adults with ASD who require a high level of support should focus on overall medical health and promotion of daily living skill building.
To assess whether a dementia care coordination intervention delays time to transition from home and reduces unmet needs in elders with memory disorders.
18-month randomized controlled trial of 303 ...community-living elders.
28 postal code areas of Baltimore, MD.
Age 70+ years, with a cognitive disorder, community-living, English-speaking, and having a study partner available.
18-month care coordination intervention to systematically identify and address dementia-related care needs through individualized care planning; referral and linkage to services; provision of dementia education and skill-building strategies; and care monitoring by an interdisciplinary team.
Primary outcomes were time to transfer from home and total percent of unmet care needs at 18 months.
Intervention participants had a significant delay in time to all-cause transition from home and the adjusted hazard of leaving the home was decreased by 37% (Hazard ratio: 0.63, 95% Confidence Interval: 0.42-0.94) compared with control participants. Although there was no significant group difference in reduction of total percent of unmet needs from baseline to 18 months, the intervention group had significant reductions in the proportion of unmet needs in safety and legal/advance care domains relative to controls. Intervention participants had a significant improvement in self-reported quality of life (QOL) relative to control participants. No group differences were found in proxy-rated QOL, neuropsychiatric symptoms, or depression.
A home-based dementia care coordination intervention delivered by non-clinical community workers trained and overseen by geriatric clinicians led to delays in transition from home, reduced unmet needs, and improved self-reported QOL.
Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory.
The ...primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety, cognitive safety, and tolerability.
The Citalopram for Agitation in Alzheimer Disease Study (CitAD) was a randomized, placebo-controlled, double-blind, parallel group trial that enrolled 186 patients with probable Alzheimer disease and clinically significant agitation from 8 academic centers in the United States and Canada from August 2009 to January 2013.
Participants (n = 186) were randomized to receive a psychosocial intervention plus either citalopram (n = 94) or placebo (n = 92) for 9 weeks. Dosage began at 10 mg per day with planned titration to 30 mg per day over 3 weeks based on response and tolerability.
Primary outcome measures were based on scores from the 18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC). Other outcomes were based on scores from the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory (NPI), ability to complete activities of daily living (ADLs), caregiver distress, cognitive safety (based on scores from the 30-point Mini Mental State Examination MMSE), and adverse events.
Participants who received citalopram showed significant improvement compared with those who received placebo on both primary outcome measures. The NBRS-A estimated treatment difference at week 9 (citalopram minus placebo) was -0.93 (95% CI, -1.80 to -0.06), P = .04. Results from the mADCS-CGIC showed 40% of citalopram participants having moderate or marked improvement from baseline compared with 26% of placebo recipients, with estimated treatment effect (odds ratio OR of being at or better than a given CGIC category) of 2.13 (95% CI, 1.23-3.69), P = .01. Participants who received citalopram showed significant improvement on the CMAI, total NPI, and caregiver distress scores but not on the NPI agitation subscale, ADLs, or in less use of rescue lorazepam. Worsening of cognition (-1.05 points; 95% CI, -1.97 to -0.13; P = .03) and QT interval prolongation (18.1 ms; 95% CI, 6.1-30.1; P = .01) were seen in the citalopram group.
Among patients with probable Alzheimer disease and agitation who were receiving psychosocial intervention, the addition of citalopram compared with placebo significantly reduced agitation and caregiver distress; however, cognitive and cardiac adverse effects of citalopram may limit its practical application at the dosage of 30 mg per day.
clinicaltrials.gov Identifier: NCT00898807.
Previous studies have shown that high serum ceramides are associated with memory impairment and hippocampal volume loss, but have not examined dementia as an outcome. The aim of this study was to ...examine whether serum ceramides and sphingomyelins (SM) were associated with an increased risk of all-cause dementia and Alzheimer disease (AD).
Participants included 99 women without dementia aged 70-79, with baseline serum SM and ceramides, enrolled in a longitudinal population-based study and followed for up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to all-cause dementia and AD using discrete time Cox proportional survival analysis. Lipids were analyzed using electrospray ionization tandem mass spectrometry.
Twenty-seven (27.3%) of the 99 women developed incident dementia. Of these, 18 (66.7%) were diagnosed with probable AD. Higher baseline serum ceramides, but not SM, were associated with an increased risk of AD; these relationships were stronger than with all-cause dementia. Compared to the lowest tertile, the middle and highest tertiles of ceramide d18:1-C16:0 were associated with a 10-fold (95% confidence interval CI 1.2-85.1) and 7.6-fold increased risk of AD (95% CI 0.9-62.1), respectively. The highest tertiles of ceramide d18:1-C24:0 (hazard ratio HR = 5.1, 95% CI 1.1-23.6) and lactosylceramide (HR = 9.8, 95% CI 1.2-80.1) were also associated with risk of AD. Total and high-density lipoprotein cholesterol and triglycerides were not associated with dementia or AD.
Results from this preliminary study suggest that particular species of serum ceramides are associated with incident AD and warrant continued examination in larger studies.
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